β-thalassemia major (β-TM) is an autosomal recessive disorder in which β-globin chain synthesis is severely decreased or absent which lead to blood transfusion dependency with its catastrophic complications. Polymorphisms at position -158 of XmnI-HBG2 on chromosome 11 and BCL11A site on chromosome 2p16 might be associated with elevated hemoglobin F (HbF) expression which may,in turn,improve β-thalassemia severity
This study aims to explore the modifying effects of XmnI and BCL11A loci on HbF levels in Egyptian β-thalassemia patients
A prospective case-control study of 70 multi-transfused β-thalassemia major patients and 22 controls was conducted in Paediatric hematology unit of Assiut university hospital from January 2016 till April 2017. PCR-RFLP was used for detection of single nucleotide polymorphisms at XmnI and BCL11A site loci.
XmnI Polymorphism detected in 9 of 70 patients and associated with higher mean HbF levels (53.48%) than patients without polymorphism (meanHbF level was 42.23%)(P-Value = 0.035).The frequency of CT heterozygousgenotype was 8(11.4%), TT homozygous genotype was (1.4%) while the wild genotype CC detected in 61 (87.1%) of the cases. While BCL11A Polymorphism detected in 21 of 70 patients had no effect on either Hb or HbF levels (P-Value = 0.26). The TT genotype frequency was 49 (70%) and TC heterozygous genotype was detected in 21 (30 %) of patients. The CC genotype was absent.
The presence of XmnI polymorphism rather than BCL11A polymorphism has a modifying effect on HbF production and increased Hb levels between β-TM patients and so, it helps in identifying patients’ benefits from HU therapy.